Method for manufacturing a fiber-reinforced bioactive ceramic implant

ABSTRACT

The invention relates to a method for manufacturing a fiber-reinforced bioactive ceramic implant, wherein a base form is made from fibrous material and interspaces between the different fibers are filled using chemical vapor phase infiltration. Preferably, a calcium-phosphate compound is brought between the fibers, which are preferably of the continuous-fiber type.

BACKGROUND OF THE INVENTION

This invention relates to a method for manufacturing a fiber-reinforcedbioactive ceramic composite material, and to the use of this material asimplant.

In the prior art different materials have already been proposed formaking implants therefrom for incorporation into animal bodies, and inparticular into the human body. Such materials are required to meetvarious, highly stringent standards.

In the first place, these materials must be biocompatible, in order thatrejection phenomena in the body do no occur or do so to the leastpossible extent.

Further, certain mechanical properties are required, specific mentionbeing made of a high toughness of fracture and a low modulus ofelasticity comparable to that of human bone tissue.

Many of the bone implants used heretofore are made of metal. Apart fromthe mechanical properties of metal, which do not correspond to adesirable extent with those of animal bone tissue, such implants must bereplaced after 10 to 15 years owing to corrosion, which is an evidentdisadvantage.

The current generation of polymeric materials which have been developedfor implantation purposes possess a desired toughness. However, thebiocompatibility of these materials leaves to be desired, so thatrejection phenomena cannot be precluded.

Ceramic materials, by contrast, are eminently biocompatible. This holdsin particular for calcium-phosphate-ceramics. However, ceramic materialshave as a disadvantage that they have a brittle fracturing behavior.

It has been proposed in the prior art to improve the toughness offracture of ceramic material by incorporating fibers. It is in thisfield that the present invention resides.

The known methods for manufacturing fiber-reinforced ceramic materialfor implantation purposes have a number of evident disadvantagesassociated with the filling of the spaces between the fibers withceramic material. This filling of the spaces between the fibers withceramic material will be designated in this description by the term"densification".

According to the first methods for manufacturing fiber-reinforcedceramic material, a fiber construction was contacted with powderedprecursor material for forming ceramics. Then this whole was subjectedto a sintering step, with ceramic being formed from the precursormaterial. This sintering step, however, has as an important disadvantagethat it entails much shrinkage and hence deformation of the productcontemplated. This occurrence of shrinkage makes the near-net-shapeformation of the implants considerably more difficult. Indeed, it is ofgreat importance for the bio-implant to have exactly the rightdimensions, especially so because the finished ceramic product does notreadily allow of any mechanical processing operation.

A general description of this type of conventional techniques formanufacturing ceramic matrix composites is given in K. K. Chawla,"Ceramic matrix composites", Chapman & Hall, London (1993), Chapter 4:"Processing of ceramic matrix composites". Further, reference is made toT. N. Tiegs, P. F. Becker, "Sintered Al₂ O₃ --SiC-whisker composites",Am.Ceram.Soc.Bull. 66 [2] (1987) 339-342. In this article Al₂ O₃ powderis mixed with SiC whiskers (monocrystal fibers of a diameter of about0.6 μm and a length of 10-80 μm) and other additions. A liquid medium isadded, followed by drying, pressing and sintering under an argonatmosphere (1 atm.) at 1700-1800° C. The shrinkage and deformationproblem to which reference is made, is discussed, for instance, in thestandard ceramic processing reference J. S. Reed, "Introduction to theprinciples of ceramic processing", John Wiley & Sons, New York (1988),Chapter 26: Firing processes.

A densification technique which has been developed to solve the problemof shrinkage is the so-called "hot pressing". In this technique thesintering step is carried out under such pressure that volumecontraction hardly occurs, if at all. However, hot pressing isapplicable to a limited extent only, because only simply shapes can bemanufactured. Again, reference is made to Chapter 26 of the Reedtextbook.

In addition, it is known that fibrous structures can be densified by thesol/gel technique. In such a technique the fibrous material is contactedwith a colloidal solution of the starting materials for the ceramicdensification material. By evaporation this solution is converted to ahomogeneous gel. The gel is then converted to a solid material byheating at high temperatures in the presence of oxygen.

These steps must be repeated a number of times because the respectivetransitions from sol to gel to solid successively entail volumereductions. In practice, it has been found that it is not possible withthis technique to fully close the spaces between the fibers. This givesrise to weak spots in the fiber-reinforced ceramic material, which cancause fracture upon loading. (A. Nazeri, E. Bescher, J. D. Mackenzie,"Ceramic composites by the sol-gel method: a review",Ceram.Eng.Sci.Proc. 14 [11-12] (1993) 1-19)

In addition, techniques are known for applying a ceramic layer to ashaped substrate. For instance, in the article by Spoto et al. in J.Mater. Chem. 4 (1994) 1849-1850 and in the article by Allen et al. inNuclear Instruments & Methods in Physics Research, Section B: BeamInteractions with materials and Atoms, p. 116 (1996) pages 457-460,methods are described for coating a substrate with hydroxyapatite byChemical Vapor Deposition (CVD). Thus a coating is formed which consistsof a different material than the substrate to which it has been applied.In such products which possess a layered structure, the bond between thedifferent materials remains a critical point. All this limits the use ofthese products for implantation purposes.

In fact, in the body many implants are exposed to a high degree ofloading, with a large number of different forces acting on the implant.Owing to differences in the mechanical properties of the materialsapplied onto each other, the bond is thereby weakened. The bond may evenbe broken, with all adverse consequences for a patient.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a homogeneousfiber-reinforced bioactive ceramic product that can be used forimplantation purposes, and which does not present the problems of theprior art. The term `bioactive implant` in this description and theappended claims is understood to mean an implant provoking a specific,biological reaction at the interface between the tissue of an organismand the implant material, which reaction results in the formation of abond between the tissue and the implant material. Physicalcharacteristics of bioactive implant include a mechanically strong bondwith surrounding, living tissue and provide a means of helping a body ina recovery process.

This object is achieved by densifying a fiber structure using chemicalvapor phase infiltration.

DETAILED DESCRIPTION OF THE INVENTION

Accordingly, the invention relates to a method for manufacturing afiber-reinforced bioactive ceramic material, wherein a base form is madefrom a fibrous material and interspaces between the different fibers arefilled using chemical vapor phase infiltration.

Using the method according to the invention the densification of a fiberpreform is carried out with chemical vapor phase infiltration (CVI).Since this technique does not entail any sintering step, the problem ofshrinkage does not arise.

In this technique the ceramic material is brought between the fibers ona molecular level. Strength problems arising through the introduction ofliquid or gel-like media, in particular the unintended and uncontrolledcreation of (macro)pores, can therefore be prevented.

It is noted that the chemical vapor phase deposition process is knownper se. This technique has been developed from the CVD process. While inthe CVD process a layer is applied to the substrate, in CVI a substrateis uniformly impregnated. Fibers are coated with material deposited froma vapor until the spaces between the fibers are filled up.

Such a technique has been described by Y. G. Roman and R. A. Terpstra ina review article in Ceramic Technology International 1996, 113-116, Ed.Ian Birkby; Sterling Publications Ltd. London.

This article describes ceramics reinforced with continuous fibers andpresently used in the aerospace industry.

In CVI a porous substrate, for instance a fiber structure, isinfiltrated with a gas phase in a reactor. In this gas phase thecomponents are present which are needed for the ceramic product to beformed. Then the elements in the gas phase are excited in such a mannerthat they react to form a solid product on the fiber surface.

An important condition for carrying out CVI is finding suitable reactionconditions under which a uniform deposition can be achieved atacceptably high reaction rates in the complete volume between the fibersof a preform.

It is preferred to use a starting substance which contains all matrixelements. In the case of an SiC-matrix the starting material is, forinstance, SiCH₃ Cl₃.

For forming a biocompatible bioactive ceramic material, in particularcalcium-phosphate compounds, suitable single-source precursors are notavailable. Specifically, calcium- and phosphorus-containing compoundsare not volatile enough, not stable enough and/or unsuitable incomposition to deposit a desired compound.

Little is known about depositing metal phosphates by chemical vaporphase reactions, using a single-source precursor. As far as is known,only the deposition of chromium, molybdenum and tungsten phosphates fromthe complex of the formula M(CO)₅ (PH)₃, wherein M represents Cr, Mo orW, has been described (I. M. Watson et al. Thin Solid Films 201 (1991),337). Corresponding complexes of calcium are not known.

According to the present invention, presently suitable gas mixtures andsuitable reaction conditions have been found which enable themanufacture of fiber-reinforced bioactive ceramics, with the spacesbetween the fibers being densified with calcium-phosphate compounds.

The ceramic material that is used according to the invention to densifythe spaces between the fibers are salts of the general formula

    Ca.sub.p (PO.sub.4).sub.q (CO.sub.3).sub.r (OH).sub.s F.sub.t

wherein p≧1 and q, r, s and t≧0, and

wherein 2p=3q+2r+s+t. When p=10, q=6, r=0, s=2 and t=0, theabove-mentioned formula gives the structural formula of hydroxyapatite,which is preferably used. If p=1, q=0, r=1 and s=0 calcium carbonate isrepresented; and when, for instance, p=9, q=5, r=1 and s=1 and t=0 acarbonate-containing hydroxyapatite is obtained. (E. J. Donahue, D. M.Schleich, Mat.Res.Bull. 26 (1991) 1119-1126, describe vapor phaseprocesses whereby CaO and CaCO₃ are deposited from Ca(dpm)₂(=Ca(tmhd)₂).

From the prior art CVD processes are known whereby specificallycalcium-containing superconductive materials, such as Tl₂ Ba₂ CaCu₂O_(x) and Bi₂ Sr₂ CaCu₂ O_(x), are deposited from the vapor phase. Thecalcium precursors used here, viz. fluorine-free and fluorine-containingCa-β-diketonates, are also usable in the method according to theinvention.

In this light reference can be made to L. M. Tone, D. W. Richeson, T. J.Marks, J. Zhao, J. Zhang, B. C. Wessels, H. O. Marcy, C. R. Kannewurf,"Organometallic chemical vapor deposition Strategies and progress in thepreparation of thin films of superconductors having high criticaltemperatures", Adv. Chem. Series 226 (1990), 351-368. Here acalcium-β-diketonate, Ca(dpm)₂, is used as calcium precursor for thedeposition of the systems Tl--Ba--Ca--Cu--O and Bi--Sr--Ca--Cu--O. Theseparate known fluorine-free and fluorine-containing Ca-β-diketonateprecursors can be used separately in the method according to the presentinvention.

In a preferred embodiment the starting material is a gas mixture inwhich either Ca(tmhd)₂ (calciumbis-2,2,6,6-tetramethyl-3,5-heptanedionate; identical to Ca(dpm)₂,calcium dipivaloylmethane), or Ca(hfac)₂ (calciumbis-1,1,5,5,5-hexafluoro-2,4-pentanedionate), preferably Ca(hfac)₂·triglyme or Ca(hfac)₂ ·tetraglyme, is used as calcium precursor.

Ca(tmhd)₂ contains only calcium, carbon, oxygen and hydrogen atoms. Thiscompound is preferably used for the formation of hydroxyapatite. Fromthis product CaO is deposited. Ca(tmhd)₂ is commercially available, forinstance from Aldrich. However, the inventors have found that thequality of this commercially available product is not sufficient fordepositing a pure product. A prior purification by sublimation, wherebythe sublimate is maintained under a dry nitrogenous atmosphere istherefore desired. For that matter, it is also possible to synthesizeCa(tmhd)₂ under dry conditions from pure CaH₂ and Htmhd.

Ca(hfac)₂, in triglyme or tetraglyme form, also contains fluorine atomsand deposits CaF₂. It is useful for depositing fluorapatite. Theseproducts can be synthesized by a one-on-one reaction of Ca(hfac)₂ withtriglyme and tetraglyme, respectively, for instance according toEuropean patent application 90201485.1.

Other suitable precursors of calcium are fluorine-free andfluorine-containing Ca-β-diketonate compounds and triglyme andtetraglyme complexes thereof such as Ca[RC(O)CHC(O)R']₂,Ca[RC(O)CHC(O)R']₂.triglyme and Ca[RC(O)CHC(O)R']₂.tetraglyme, wherein,for instance, (fluorine-free) R=R'=CH₃ ; R=R'=t--Bu; R=CH₃, R'=tBu; and,for instance (fluorine-containing) R =R'=CF₃ ; R=CH₃, R'=CF₃ ; R=n-C₃F₇, R'=tBu. See: European patent applications 90201485.1 and 92307490.0.

As already indicated hereinabove, not much is known about the vapordeposition of metal phosphates. In the above-mentioned article by Spotoet al. in J. Mater. Chem. P₂ O₅ is used as source of phosphorus. Thiscompound has an evaporation temperature of 270° C.

Phosphorus precursors that have a lower evaporation temperature arealkyl phosphites of the general structure P(OR)₃ or alkyl phosphates ofthe general structure OP(OR)₃, wherein R represents a low, C₁₋₆saturated or unsaturated and/or branched alkyl group, and preferablymethyl or ethyl. In addition, the chlorine-containing compounds PCl₃ andPOCl₃ can be used as phosphorus precursor, although these compounds arerather hydrolysis-sensitive.

By starting from pure starting material, very pure bioceramics can bemade.

In the method according to the invention first a base form of fibrousmaterial is made. This base form determines the eventual shape of theimplant to be manufactured. The spaces between the fibers are filled up.

In fact, any fibrous material that is compatible with the ceramics to beinfiltrated and that is stable during the reaction conditions during theCVI step can be used. Specifically, ceramic fibers, glass fibers, carbonfibers and organic polymeric fibers are suitable, preferably fibers ofcarbon, hydroxyapatite, aluminum oxide, zirconium oxide, glass or metalfibers, such as inter alia Fecralloy®.

The method according to the invention makes it possible to employ longor continuous fibers as fibrous material. This provides great advantagesas regards the mechanical properties, in particular toughness, of theimplant to be manufactured.

At the relatively high sintering temperature such as it is employed inthe known sintering technique, by contrast, the continuous fibers lose alarge part of their mechanical properties owing to growth of granulesand creep. If during such a densification in addition high pressures(hot pressing) are employed, the fibers will further be subjected tomechanical loading as well and consequently fracture and sustain damage.Obviously, this is not beneficial to the properties of the composite.

Through a suitable choice of the type and the orientation of the fibrousmaterial, the stiffness (modulus) of the implant can be optimized in anydesired direction.

The base form, which must possess a certain dimensional stability, canbe manufactured in a conventional manner, for instance using textiletechniques. See, for instance, F. K. Ko, "Preform fibre architecture forceramic matrix composites", Ceramic Bulletin 68 [2] (1989) 4021-413.

In the reactor, in which a base form from fibrous material is present,gaseous precursors for the ceramics are introduced. By choosing thepressure of the gas streams and the reactor temperature to be favorable,the gases diffuse through the base form of fibrous material. In the baseform the gases react to form a solid. It is of great importance herethat the conditions are selected such that the matrix depositshomogeneously in the entire volume of the fibrous substrate withacceptable rates.

The method according to the invention, wherein a base form from fibrousmaterial is densified with a ceramic material, has as an advantage thatit is carried out under mild conditions, such as a relatively lowdensification temperature. As a result, the fibrous structure is not, atleast less readily, damaged. The infiltration or densificationtemperature in the CVI reactor is between 200 and 1200° C., preferablybetween 300 and 900° C., most preferably between 350 and 800° C. Theinfiltration or densification temperature can be set at a value duringthe reaction, that is, can follow a gradient. The pressure in the CVIreactor is preferably between 1 mbar-5 bar (absolute), preferablybetween 1 mbar and 1 bar (absolute). The precursor mole fraction ispreferably between 0.05 and 1, preferably between 0.5 and 1, while thetotal gas flow regime is preferably between 1 ml/min to 10,000 ml/min(STP) and more preferably between 100 and 1000 ml/min (STP).

It is noted that international patent application 90/08745 discloses amethod in which a form part based on pyrocarbon is manufactured. Thisform part, which can be used in cardiac valves, is manufactured bycoking carbon fibers at 800-1200° C. and subsequently infiltrating thisproduct with pyrocarbon at about 1100° C., whereafter the product issealed with a layer of pyrocarbon at a temperature of between 1300 and1800° C. Such carbon-carbon composites cannot actively participate inprocesses in the body and are therefore not bioactive. Further, duringthe high infiltration temperatures the fibers lose a great part of theirmechanical properties, so that the composite end product is notcomparable in terms of properties with the products that are obtainedaccording to the invention.

The method of the invention makes it possible to control the porosity ofthe infiltrated material without the mechanical properties beingadversely affected. In particular, this occurs by slowly growing aceramic coating on the fibers. According as the infiltration lastslonger, the coating grows on longer, until the complete porosity isfilled up. By ending the infiltration process prematurely, the compositestill retains a certain porosity. Moreover, by selecting the properprocess conditions, the manner in which the growth proceeds in terms ofpore size distribution can be controlled as well. Some degree ofporosity provides that a better bonding between the implant and tissueis accomplished. In particular, some degree of porosity provides thepossibility of systemic tissue growing in.

According to a preferred embodiment, the fibrous material is densifiedin two steps, the first step consisting in carrying out a sol/geltechnique, and the second step consisting in carrying out CVI. Thisembodiment provides a method which allows the densification to becarried out faster. First a coarse infiltration with a sol/geltechnique, for instance that described in the publication of Takahashiet al. in Eur. J. Solid State Inorg. Chem. 32 (1995) 829-835, is carriedout, whereafter the coarse structure is further densified using CVI.

The present invention will now be elucidated in and by the following,non-limiting examples.

EXAMPLE 1

Use is made of the apparatus described in Chapter 3 of theabove-mentioned thesis by Roman. Two-dimensional wovens of carbon fibers(Toray Industries Inc.; Torayra T-300) are wetted with acetone toprevent breakage of the fibers. Thereafter these wovens are cut to sizeand stacked onto each other, with the successive layers having adifferent orientation relative to each other (turned through 45°relative to the preceding layer), in order to obtain as much isotropy aspossible. These stacked layers constitute the preform. The preform isplaced in a graphite holder.

In the underside of this preform holder, holes have been drilled to leadgaseous/vaporous reactants into the preform. The top of the preformholder, which is open in known applications, is closed off with a(graphite) cover in which holes have been drilled to lead unreactedreactants and gaseous/vaporous reaction products out of the preform. Thecover can be screwed fixedly to the preform holder, with the preformitself being compressed. Then the preform holder/preform combination iswashed with acetone three times for 30 minutes, after which thecombination is dried under vacuum, at a good 150° C. for three hours.Then the preform holder/preform combination is mounted on the gasinjector, in such a manner that gas from the injector can only flowthrough the preform holder. The reactor chamber in which the preform isdisposed is evacuated by suction, and the reactor chamber is brought tothe desired temperature of 850° C. via the surrounding oven at aconstant heating rate of 2° C./min.

When the reactor chamber has reached the desired temperature (measuredwith thermocouples), the pressure in the chamber is adjusted to thedesired value of 50 Torr. The separate calcium precursor Ca(tmhd)₂ andfluorine precursor P(OCH₃)₃, which are located outside the reactorchamber, are heated to 210° C. and 80° C., respectively, so that theirvapor pressures are sufficiently high. The carrier gas is passed throughthe precursors. The vapor flow is controlled with a calibrated "vaporsource controller". Then the gas/vapor mixture is passed to the injectorat a flow rate of 500 ml/min. Under the influence of the hightemperature the vaporous reactants are converted to a solid material,precipitated on the fibers of the preform. Standard analyses show theprecipitate formed consists substantially of hydroxyapatite.

What is claimed is:
 1. A method for manufacturing a fiber-reinforcedbioactive ceramic implant, comprising the steps ofa) preparing a baseform of continuous fibers having spaces therebetween constituting anopen volume, and then b) infiltrating the base form with calcium- andphosphate-containing gas precursors by applying a gradient over saidbase form so that said gas precursors pass through said base form, c)exciting the gas precursors to form a solid ceramic product on all ofthe fibers throughout the base form, wherein the ceramic homogeneouslyfills the open volume to thereby densify the base form,wherein theinfiltrating and exciting steps are carried out over a period of timelimited so as to retain a desired degree of porosity.
 2. A methodaccording to claim 1, wherein the gas precursor comprises calciumbis-1,1,5,5,5-hexafluoro-2,4,-pentanedionate·triglyme or tetraglyme. 3.A method according to claim 1, wherein the gas precursor comprises aphosphorus source chosen from the group consisting of an alkylphosphite, an alkyl phosphate, a phosphorus-chlorine compound and P₂ O₅.4. A method according to claim 1, wherein the fibrous material comprisescontinuous fibers.
 5. A method according to claim 1, wherein theinfiltrating step is carried out in a CVI reactor, at a temperaturebetween 300 and 1200° C.
 6. A method according to claim 5, wherein thepressure in the CVI reactor is between 1 mbar and 5 bar (abs.).
 7. Amethod according to claim 1, further comprising the step of, prior todensification with chemical vapor phase infiltration, initiallydensifying the base form using a sol/gel technique.
 8. The method ofclaim 1, wherein the gradient is chosen from the group consisting of atemperature gradient, a pressure gradient, and a combination thereof.